Huan Wang

© 2015, The Author.Purpose: A male infant developed generalized rash, intestinal inflammation and severe infections including persistent cytomegalovirus. Family history was negative, T cell receptor excision circles were normal, and engraftment of maternal cells was absent. No defects were found in multiple genes associated with severe combined immunodeficiency. A 9/10 HLA matched unrelated hematopoietic cell transplant led to mixed chimerism with clinical resolution. We sought an underlying cause for this patient’s immune deficiency and dysregulation. Methods: Clinical and laboratory features were reviewed. Whole exome sequencing and analysis of genomic DNA from the patient, parents and 2 unaffected siblings was performed, revealing 2 MALT1 variants. With a host-specific HLA-C antibody, we assessed MALT1 expression and function in the patient’s post-HCT autologous and donor lymphocytes. Wild type MALT1 cDNA was added to transformed autologous patient B cells to assess functional correction. Results: The patient had compound heterozygous DNA variants affecting exon 10 of MALT1, a maternally inherited splice acceptor c.1019-2A > G, and a de novo deletion of c.1059C leading to a frameshift and premature termination. Autologous lymphocytes failed to express MALT1 and lacked NF-κB signaling dependent upon the CARMA1, BCL-10 and MALT1 signalosome. Transduction with wild type MALT1 cDNA corrected the observed defects. Conclusions: Our nonconsanguineous patient with early onset profound combined immunodeficiency and immune dysregulation due to compound heterozygous MALT1 mutations extends the clinical and immunologic phenotype reported in 2 prior families. Clinical cure was achieved with mixed chimerism after nonmyeloablative conditioning and HCT.

© 2015 The Authors. Through the use of bulk measurements in metabolic organs, the circadian clock was shown to play roles in organismal energy homeostasis. However, the relationship between metabolic and circadian oscillations has not been studied invivo at a single-cell level. Also, it is unknown whether the circadian clock controls metabolism in stem cells. We used a sensitive, noninvasive method to detect metabolic oscillations and circadian phase within epidermal stem cells in live mice at the single-cell level. We observe a higher NADH/NAD+ ratio, reflecting an increased glycolysis/oxidative phosphorylation ratio during the night compared to the day. Furthermore, we demonstrate that single-cell metabolic heterogeneity within the basal cell layer correlates with the circadian clock and that diurnal fluctuations in NADH/NAD+ ratio are Bmal1 dependent. Our data show that, in proliferating stem cells, the circadian clock coordinates activities of oxidative phosphorylation and glycolysis with DNA synthesis, perhaps as a protective mechanism against genotoxicity.

ObjectiveBasic combat training is a kind of necessary high-intensity training to help each military recruit convert into a qualified soldier. In China, both the physical fatigue and passive psychological state have been observed in new recruits during BCT. However, after same-intensity training, the degree of fatigue and passive mood vary among recruits. Therefore, this study aimed to explore the effect of BCT on mood state of recruits with different physical fitness levels from a perspective of fatigue.Materials and methodsBefore and after BCT, the degree of fatigue and mood state of participants were evaluated via the Borg Rating of Perceived Exertion Scale and Profile of Mood States Questionnaire immediately after 20 push-ups as RPE and POMS scores [total mood disturbance, passive mood and positive mood ]. The participants were divided into two groups according to the RPE score measured after BCT: group 1: RPE score after BCT < 13 and group 2: RPE score after BCT ≥ 13.ResultA total of 564 recruits were included. After BCT, in group 1, TMD and passive mood Ttension, Tfatigue, Tdepression, Tconfusion declined significantly, but positive mood both increased significantly ; while in group 2, only Tanger and Testeem increased significantly.ConclusionBCT could alleviate passive mood and add to positive mood for recruits with better physical fitness, while had no ameliorative effects on or even deteriorate most of the passive mood for recruits with worse physical fitness.

Social impact bonds have emerged as an innovative financial instrument designed to support the social service sector in delivering innovative social programs. In particular, SIBs can be used to finance prevention of homelessness among those regarded as vulnerable. There is little evidence that outcomes from SIB-funded programs are significantly different compared to more traditional programs. This is the first scoping review of academic and gray literature that explores the main features and outcomes from all SIBs for homelessness based on evidence, addressing an important gap in the literature. The scoping review provides a transparent and comprehensive approach for mapping areas of this research. A total of 73 studies and articles were found eligible for inclusion. These concerned 32 SIBs for homelessness implemented in the United Kingdom, the United States, Australia, and Belgium. The review found that academic papers on SIBs for homelessness lack evidence-based analysis, while gray literature lacks transparency, especially in evaluation method and outcome. We found that fourteen projects met their target outcomes. The common features of these SIBs were a navigator intervention model, effective partnership working, and use of Special Purpose Vehicles. Our findings show that it is necessary for the managers of SIBs to improve outcome metrics and evaluation methods, support target groups fairly, and attract more private investors to finance SIBs for better addressing homelessness.